Neuroplastic Alterations of the Motor Cortex by Caffeine

NCT04011670 | Completed DMC

• 1 other identifier: 33/3/19
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Caffeine is a psychostimulant drug. It acts as a competitive antagonist at adenosine receptors, which modulate cortical excitability as well. In deep brain stimulation (DBS), the production of adenosine following the release of adenosine triphosphate (ATP) explains the reduction of tremor. Binding of adenosine to adenosine A1 receptors suppresses excitatory transmission in the thalamus and hereby reduces both tremor-and DBS-induced side effects. Also, the effect of adenosine was attenuated following the administration of the 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) adenosine A1 receptor antagonist. Therefore, the presence of a receptor antagonist such as caffeine was suggested to reduce the effectiveness of deep brain stimulation (DBS) in treating tremor and other movement disorders. Based on this finding, the investigators hypothesize that the antagonistic effect of caffeine can tentatively block the excitatory effects of transcranial alternating current stimulation (tACS). The plasticity effects might differ among caffeine users and non- caffeine users depending on the availability of receptor binding sites. Apart from that, a major issue in NIBS studies including those studying motor-evoked potentials is the response variability both within and between individuals. The trial to trial variability of motor evoked potentials (MEPs) may be affected by many factors. Inherent to caffeine is its effect on vigilance. In this study, the investigator shall monitor the participant's vigilance by pupillometry to (1) better understand the factors, which might cause variability in transcranial excitability induction studies and (2) to separate the direct pharmacological effect from the indirect attentional effect of caffeine.

Conditions

Cortical Excitability; Brain Stimulation; Caffeine

Keywords

Plasticity; Variability; Non-invasive brain stimulation; Caffeine

Outcome Measures

Primary Outcomes (2)

• Neuroplastic changes of the cortical areas

  Motor cortex plasticity is measured from the changes in the amplitude of the motor evoked potentials (MEPs) at different time points. Transcranial magnetic stimulation (TMS) will be used to measure MEP amplitudes.

  Baseline (pre-measurement), immediately after intervention, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes

• The influence of vigilance during stimulation

  Participant's level of vigilance is monitored from pupil diameter and pupil unrest index (PUI) using pupillometer. This measurement is carried out during 10 minutes of transcranial alternating current stimulation (tACS)

  10 minutes

Secondary Outcomes (1)

• Genetic polymorphism

  1 year

Study Arms (2)

Caffeine group

ACTIVE COMPARATOR

Participants will receive a caffeine tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition.

Other: 200 mg caffeine tablet

Placebo group

PLACEBO COMPARATOR

Participants will receive a placebo tablet and all electrical stimulations in a random order (tACS 140 Hz at 1 mA and sham tACS). Participant's vigilance status will be monitor based on active vigilance condition or passive vigilance condition.

Other: Non-active tablet

Interventions

200 mg caffeine tablet OTHER

* Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition

Caffeine group

Non-active tablet OTHER

* Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and active vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) at 1 mA and passive vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) sham and active vigilance condition * Transcranial alternating current stimulation (140 Hz tACS) sham and passive vigilance condition

Placebo group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female healthy participants between the ages of 18-45.
• Right-handed (Oldfield 1971).
• Free willing participation and written, informed consent of all subjects obtained prior to the start of the study.
• Participant's weight is above 60 kg

You may not qualify if:

• Age \< 18 or \> 45 years old;
• Left hand dominant;
• Evidence of a chronic disease or history with a disorder of the nervous system
• History of epileptic seizures;
• Pacemaker or deep brain stimulation;
• Metal implants in the head region (metal used in the head region, for example, clips after the operation of an intracerebral aneurysm (vessel sacking in the region of the brain vessels), implantation of an artificial auditory canal);
• Cerebral trauma with loss of consciousness in prehistory;
• Existence of a serious internal (internal organs) or psychiatric (mental illness)
• Alcohol, medication or drug addiction;
• Receptive or global aphasia (disturbance of speech comprehension or additionally of speech);
• Participation in another scientific or clinical study within the last 4 weeks;
• Pregnancy
• Breastfeeding
• Intolerance to caffeine or coffee products
• Participant who has abnormal heart activity from an electrocardiography (ECG) finding

Sponsors & Collaborators

• University Medical Center Goettingen: lead

Study Sites (1)

Prof. Dr. Walter Paulus

Goettigen, Lower Saxony, 37075, Germany

Location

Related Publications (29)

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• Polania R, Nitsche MA, Korman C, Batsikadze G, Paulus W. The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol. 2012 Jul 24;22(14):1314-8. doi: 10.1016/j.cub.2012.05.021. Epub 2012 Jun 7.

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• Zulkifly MFM, Merkohitaj O, Brockmoller J, Paulus W. Confounding effects of caffeine on neuroplasticity induced by transcranial alternating current stimulation and paired associative stimulation. Clin Neurophysiol. 2021 Jun;132(6):1367-1379. doi: 10.1016/j.clinph.2021.01.024. Epub 2021 Mar 10.

  PMID: 33762129 DERIVED

• Zulkifly MFM, Merkohitaj O, Paulus W, Brockmoller J. The roles of caffeine and corticosteroids in modulating cortical excitability after paired associative stimulation (PAS) and transcranial alternating current stimulation (tACS) in caffeine-naive and caffeine-adapted subjects. Psychoneuroendocrinology. 2021 May;127:105201. doi: 10.1016/j.psyneuen.2021.105201. Epub 2021 Mar 15.

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MeSH Terms

Interventions

Caffeine

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Walter Paulus

  University Medical Center Goettingen, Goettingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: A statistician prepares a randomization list. Only the pharmacist knows the medication type (caffeine or placebo) and the type of electrical stimulation. The researcher knows only the vigilance conditions (\*\*passive or \*active) . An investigator is blinded to the type of electrical stimulation and medication. In addition, all participants are naive to electrical stimulation and do not know if they receive placebo or verum drug.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department for Clinical Neurophysiology

Model Details: 15 participants are assigned to caffeine group and another 15 are assigned to placebo group. Then, the participants who were initially in the caffeine group now be in placebo group and those who were in the placebo group were assigned to caffeine group. Finally, all participants received both placebo and caffeine

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: July 8, 2019
• Study Start: July 15, 2019
• Primary Completion: November 19, 2019
• Study Completion: November 19, 2019
• Last Updated: November 29, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)